The Impact of Exercise on Gut Microbiota in a Survivor to Germ-free Mouse Translational Model of Breast Cancer
Date
2021-12-17
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Abstract
Breast cancer is the leading cause of global cancer incidence. Strategies to improve breast cancer treatment and health outcomes in survivors are needed to decrease mortality, mitigate side effects, and prevent recurrence. The gut microbiota is altered in individuals with breast cancer, can be affected by treatments such as chemotherapy, and plays a role in response to cancer treatments. It may be modified by environmental factors such as dietary components and exercise. In the present study, the Alberta Cancer Exercise (ACE) program was investigated as a strategy to favorably modify the gut microbiota of breast cancer survivors who had undergone chemotherapy. In a follow-up germ-free mouse study, the ability of exercise-responsive gut microbiota, alone or with prebiotic fiber supplementation, to alter tumor growth was interrogated using fecal microbiota transfer (FMT). In the cancer survivors, there was a significant enrichment in Dialister, Oscillospiraceae, and Paraprevotella following exercise (p < 0.01). In the germ-free mice, tumor volume trended consistently lower over time in the groups colonized with post-exercise gut microbiota compared to the group colonized with pre-exercise gut microbiota, with statistically significant differences found on day 16 and day 22. Tumor volume was further suppressed with prebiotic fiber supplementation. Gut microbial alpha and beta diversity differed across groups. Beta diversity and differential abundance analyses revealed that both the tumor cell injection and chemotherapy altered the gut microbial community in the mice. A potentially beneficial enhancement of Parasutterella and Lachnospiraceae and depletion of Anaerostipes and Ruminococcus gnavus was identified on day 22 in the group receiving prebiotic. Cytokine analysis of tumor tissue and serum indicated that the influence of the various FMTs resulted in distinct tumor microenvironments. The tumors of mice colonized with exercise-responsive microbiota exhibited lower levels of angiogenic VEGF among other markers, and greater levels of cytokines previously associated with positive Paclitaxel response. This was augmented with prebiotic supplementation. Exercise and prebiotic demonstrated potential to enhance anti-tumor immunity through advantageous gut microbiota modulation in breast cancer populations and should be further explored as adjuvants.
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Keywords
Gut Microbiota, Exercise, Prebiotics, Nutrition, Breast Cancer
Citation
Sampsell, K. (2021). The Impact of Exercise on Gut Microbiota in a Survivor to Germ-free Mouse Translational Model of Breast Cancer (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.